Clinical experience with novel antiplatelet therapy ticagrelor:which patients benefit the most?

Maja Strozzi, Marko Noč, Robert Bernat

3rd DUBROVNIK CARDIOLOGY HIGHLIGHTS 2013, 27.09.2013.

All presentations are made on the

request of AstraZeneca, according to

valid legislative. All presentations are

nonpromotional.

Ticagrelor – who

benefits most ?

The concept ...

5

The topics

Guidelines

Evidence on ticagrelor

Evidence analysis

Subgroups who benefit most

Ticagrelor – a drug for the widest

spectrum of ACS ?

Guidelines

ACCF/AHA NSTEACS 2012

ACCF/AHA STEMI 2013

9

ESC Myocardial Revascularization 2010

10

ESC NSTEACS 2011

11

ESC STEMI 2012

•Prasugrel – TRITON-TIMI 38* (13.608)

•Ticagrelor – PLATO** (18.624)

The evidence:

* Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel

versus clopidogrel in patients with acute coronary

syndromes. N Engl J Med 2007;357:2001-15

** Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus

clopidogrel in patients with acute coronary syndromes. N

Engl J Med 2009;361:1045-57.

Evidence analysis

prasugrel ticagrelor

patient profile

older (>75y)

fragile (<60kg)

prior stroke/TIA

adverse effects

dyspnea

bradycardia

Subgroup analysis

prasugrel ticagrelor

efficacy

CV death

ACS treatment

PCI

CABG

medical

?

?

Who will benefit most ?

ACS Case

• F, 70y

• hypertension, DM, dyslipidemia, smoker

• 1.2.2013. STEMI inf.

• agregometry (patient included in a study), randomized to

standard clopidogrel dose. Results known later: clopidogrel

hypo reactor

TIMI score 4, mort. 7,6%GRACE score 141, mort.17%

STEMI 2012: antithrombotic therapy

In acute phase Ticagrelor without limitations (clopidogrel only if new ADP-

receptor blocker are not available)

Tica-grelor

HZZO

Acute STEMI

PCI result

STEMI 2012: antithrombotic therapy

In the follow up recommended over clopidogrel

IST

• referred for CABG, surgery delayed (DAPT). Finally

patient refused surgery!

• 11.2.2013. re-STEMI, IST, cardiogenic shock, AV block

III, VT, mechanic ventilation, TIA?

• rePCI, GP 2b/3a, ECG normalization in inf. leads

TIMI score 10, mort. 38,7%GRACE score 215, mort. 80%

IST

Case 2 – How would you treat ?

m, 53 y, anterior STEMI

Case 2 – How did I treat ?

1 manual aspiration, 3 wires & 2 stents later...

Case 3 – How would you treat ?

m, 71 y, s/p CABG, NSTEACS

Case 3 – How would you treat ?

on day 6 – subac. thrombosis...

Case 3 – How did we treat ?

on day 6 – subac. thrombosis, aspiration only...

PLATO study: In stent thrombosis

Patients with intent for invasive treatment

Ticagrelor (n=6732)

Clopidogrel (n=6676)

HR for ticagrelor (95% CI)

P value

Stent thrombosis, n (%)

Definite 71 (1.3) 106 (1.9)0.67 (0.50-

0.91)0.0091

Probable + Definite 118 (2.1) 158 (2.8)0.75 (0.59-

0.95)0.0167

Possible + Probable + Definite 155 (2.8) 202 (3.6)

0.77 (0.62-

0.95)0.0131

Wallentin L, et al. N Engl J Med. 2009;361:1045-1057.

Second IST

• 20.3.2013. re-re-STEMI inf

• re-re-PCI RCA, good clinical recovery, EHO – EF 40%

• stable angina III st

Second IST

high risk ACS, potential CABG, clopidogrel hypo reactor, repeat in

stent thrombosis

Stable angina 2013: antithrombotic therapy

Ticagrelor should or may be considered in some stable patients

after PCI

PLATO outcomes (early and late period)

Wallentin L. Presented at ECS congress 2009

MACE reduction benefite increase by time.

PLATO study

• Significant reduction of

cardiovascular death (4,0 to

5,1% in 12 months)

• Treating 1000 patients with

ticagrelor, 14 lives can be saved

Wallentin L, et al. N Engl J Med. 2009;361:1045-1057

My questions after PLATO

Study has shown superiority of the new drug.

Considering the price, can we give it to all ACS

patients?

Probably not

Can we identify a group of patients who would benefit

most from ticagrelor therapy?

Subgroup analysis

Wallentin L et al N Engl J med. 2009,381:1045-57

ACS patients with diabetes

James S et al. Eur Heart J. 2010 Dec;31(24):3006-16.

ACS patients with diabetes

James S et al. Eur Heart J. 2010 Dec;31(24):3006-16.

Who would benefit most?

Patients with ACS and planed early invasive strategy (less than

2 hours) because fast and consistent blockade of P2Y12

receptors

PCI patients with high potential for thrombotic events because

of significant reduction of in stent thrombosis (large thrombus

burden, suboptimal PCI result, slow TIMI flow, long stent

segment etc.) or clinical characteristic like diabetes, renal failure

etc.

Patients with stent thrombosis and documented clopidogrel

resistance.

It would be reasonable for all ACS because of significant

mortality reduction in 1 year follow up

Ticagrelor for all patients with ACS?

It would be difficult to achieve that, due to

current economic situation

Individual patient selection, what I prefer,

would be difficult to apply

We proposed Ticagrelor in all patient

undergoing urgent PCI for acute myocardial

infarction included in the "Croatian PCI

network"

Patients with in stent thrombosis and known

clopidogrel resistance are implied

Thank you.